CAJ | 학술논문

目的：他汀类药物被发现具有减轻肾病大鼠蛋白尿的作用，本研究试图证明阿托伐他汀是否通过抑制Rac1减轻肾病综合征。方法通过给SD大鼠一次性腹腔注射嘌呤毒素氨基核苷（ puromycin amino－nucleoside， PAN）的方法制备大鼠肾病综合征模型，设对照组、模型组和阿托伐他汀治疗组。免疫荧光法检测大鼠肾小球中nephrin和podocin的表达， Western印迹检测Rac1的表达。结果与正常对照组相比，模型组大鼠表现为典型的肾病综合征：尿蛋白排泄量明显增加[（199．23±68．04） mg／24 h]，血白蛋白明显降低[（15．28±1．93） g／L]，血胆固醇明显升高[（8．54±2．01） mmol／L]；阿托伐他汀治疗后显著地降低了尿蛋白[（128．49±75．61） mg／24 h]和血胆固醇[（4．23±1．44） mmol／L]而提高了血白蛋白水平[（22．45±4．24） g／L]。与正常对照组相比，模型组大鼠肾小球中nephrin和podocin表达降低，细胞膜的Rac1表达上调，他汀治疗后能上调nephrin和podocin表达以及抑制Rac1在细胞膜的表达。结论阿托伐他汀能够减轻PAN大鼠蛋白尿，减轻PAN所导致的足细胞损伤，这一效应可能是通过抑制Rac1活化来实现的。
목적：타정류약물피발현구유감경신병대서단백뇨적작용，본연구시도증명아탁벌타정시부통과억제Rac1감경신병종합정。방법통과급SD대서일차성복강주사표령독소안기핵감（ puromycin amino－nucleoside， PAN）적방법제비대서신병종합정모형，설대조조、모형조화아탁벌타정치료조。면역형광법검측대서신소구중nephrin화podocin적표체， Western인적검측Rac1적표체。결과여정상대조조상비，모형조대서표현위전형적신병종합정：뇨단백배설량명현증가[（199．23±68．04） mg／24 h]，혈백단백명현강저[（15．28±1．93） g／L]，혈담고순명현승고[（8．54±2．01） mmol／L]；아탁벌타정치료후현저지강저료뇨단백[（128．49±75．61） mg／24 h]화혈담고순[（4．23±1．44） mmol／L]이제고료혈백단백수평[（22．45±4．24） g／L]。여정상대조조상비，모형조대서신소구중nephrin화podocin표체강저，세포막적Rac1표체상조，타정치료후능상조nephrin화podocin표체이급억제Rac1재세포막적표체。결론아탁벌타정능구감경PAN대서단백뇨，감경PAN소도치적족세포손상，저일효응가능시통과억제Rac1활화래실현적。
Objective Statins have been reported to reduce the amount of urinary protein in nephrotic syndrome rats.The objective of this study was to explore whether atorvastatin ameliorates puromycin aminonucleoside ( PAN) induced nephropathy via inhibiting Rac1 signaling.Methods Rat nephrotic syndrome model was induced by intraperitoneal injection of single dose of PAN.Animals were divided into three groups: control group, model group, and atorvastatin group.The expressions of podocin and nephrin were determined by immunofluorescence, and the ex-pression of Rac1 was detected by Western blotting.Results Compared with the control group, u-rine protein excretion was extremely increased [(199.23 ±68.04) mg/24h], serum albumin levels decreased [ (15.28 ±1.93) g/L] and cholesterol level increased [ (8.54 ±2.01) mmol/L] in model group.Atorvastatin treatment obviously decreased the levels of urine protein [ ( 128.49 ± 75.61 ) mg/24h] and cholesterol [ (4.23 ±1.44) mmol/L] , and increased serum albumin level [ (22.45 ±4.24 ) g/L] .Reduction of nephrin and podocin in glomerulus and increase of mem-brane Rac1 expression were detected in model group compared with control group.After treatment of atorvastatin, the expressions of nephrin and podocin were raised, and the expression of Rac1 on the membrane was inhibited.Conlusion Atorvastatin can decrease urine protein excretion, and allevi-ate podocyte injury by inhibiting Rac1 signaling in rats with PAN-induced nephropathy.